Pressure-induced dermal lesions deriving from wide ranging circumstances present significant medical problems to individuals dependent on assistive devices. Because of the diverse situations under which these lesions occur, a generally applicable means of preventing the development of pressure or decubitus ulcers would be advantageous. This research proposal, in response to the RFA HD 93-012 entitled "Assistive Devices and Skin Integrity," is to develop a general purpose transdermal delivery system for the prevention of early dermal pressure pathology. It is a multidisciplinary approach combining the expertise of the biophysical and material scientist with that of the biochemist and veterinarian researcher. It is an interventional approach in which a relatively new class of biomaterials is to be used to deliver medication, to sites at risk, for the purpose of preventing the tissue necrosis that results whenever soft tissue is compressed between an assistive device and an bony prominence. The biochemical approach is to inhibit enzyme, thromboxane synthetase, which produces thromboxanes considered responsible for the tissue necrosis. The animal model is to be the greyhound dog which, because of its thin skin, angular body, limited body fat and hair, is predisposed to pressure ulcers similar to those occurring in humans. The proposed four-year research efforts is in the form of four research projects, each of which has a primary specific aim; namely: PROJECT I, to synthesize and develop elastomeric polypeptide biomaterials in the form of bioelastic matrices for the effective transdermal delivery of thromboxane synthetase inhibitor; PROJECT II, to establish in vitro the inhibitor penetration into and through the viable skin of the greyhound dog and human skin derived from breast reduction surgeries; PROJECT III, to evaluate in vivo the capacity of inhibitor doped bioelastic matrices to effect penetration of three widely different concentrations of medication into the skin of the greyhound; and PROJECT IV, to evaluate the effectiveness of each of the inhibitor-laden bioelastic matrices at the three coarsely different concentrations of inhibitor to prevent pressure dermal lesions in greyhound dogs wearing a short limb, coaptation, walking cast and then having determined which of the three coarse concentrations is most effective, to establish with a finer grained range of concentrations the most effective concentration for which the inhibitor-laden matrix will prevent the tissue necrosis leading to pressure ulcer. In general the projects are to run in sequence with PROJECT I continuing at a reduced level for years 2, 3 and 4 to provide inhibitor-loaded bioelastic matrices to PROJECTS II, III, and IV and to refine inhibitor time release profiles. PROJECT II is to use viable skin in vitro in a specially designed chamber for which considerable transdermal penetration studies have been carried out and PROJECTS III, and IV continue work on the short limb, cast model for the greyhound dog for which the thromboxane synthetase inhibitor given by mouth was found to be effective in reducing lesion formation.